6533b832fe1ef96bd129ad12

RESEARCH PRODUCT

Increased expression of interleukin-22 in patients with giant cell arteritis

Maria ParmeggianiMartina BonaciniAlberto CavazzaLuigi BoiardiLucia BelloniAlessandro ZerbiniCarlo SalvaraniStefania CrociAntonio MoramarcoFrancesco CicciaRiccardo AlessandroFrancesco MuratoreLuca CiminoAroldo Rizzo

subject

0301 basic medicineCD4-Positive T-LymphocytesMalearterial remodelling; autoimmunity; giant cell arteritis; inflammation; interleukin-22; pathogenesismedicine.medical_treatmentMessengerInterleukin 220302 clinical medicineimmune system diseasesarterial remodelling; autoimmunity; giant cell arteritis; inflammation; interleukin-22; pathogenesis; Aged; Aged 80 and over; CD4-Positive T-Lymphocytes; Calcium Ionophores; Carcinogens; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Giant Cell Arteritis; Humans; Immunohistochemistry; In Vitro Techniques; Interleukins; Ionomycin; Leukocytes Mononuclear; Male; RNA Messenger; Real-Time Polymerase Chain Reaction; Temporal Arteries; Tetradecanoylphorbol Acetate80 and overLeukocytesPharmacology (medical)skin and connective tissue diseasesAged 80 and overIonomycinpathogenesisautoimmunityInterleukinFlow CytometryImmunohistochemistryTemporal ArteriesCalcium IonophoresCytokinecardiovascular systemTetradecanoylphorbol AcetateFemalemedicine.symptomgiant cell arteritiStromal cellMononuclearGiant Cell ArteritisInflammationEnzyme-Linked Immunosorbent AssayIn Vitro TechniquesReal-Time Polymerase Chain ReactionPeripheral blood mononuclear cellarterial remodelling03 medical and health sciencesRheumatologymedicineHumansViability assayRNA Messengercardiovascular diseasesAged030203 arthritis & rheumatologybusiness.industryInterleukinsinterleukin-22medicine.diseaseGiant cell arteritis030104 developmental biologyinflammationCase-Control StudiesImmunologyCarcinogensLeukocytes MononuclearRNAbusiness

description

Objectives GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis. Methods Patients subjected to temporal artery biopsies (TABs) naive from therapy were enrolled: 27 biopsy-proven GCA, 8 biopsy-negative GCA, 21 biopsy-negative non-GCA patients. Expression of IL-22 was determined in TABs by immunohystochemistry, in plasma by ELISA, in peripheral blood mononuclear cells by real-time PCR and flow cytometry. Effects of IL-22 on viability and gene expression of primary cultures obtained from TABs were also evaluated. Results Inflamed TABs from GCA patients showed a higher expression of IL-22 and IL-22 specific receptor subunit (IL-22R1) than non-inflamed TABs. IL-22 was expressed in infiltrating immune cells and spindle shaped cells, IL-22R1 was expressed in endothelial cells. Patients with biopsy-proven GCA showed increased levels of IL-22 in plasma than patients with biopsy-negative GCA, without GCA and healthy subjects. Peripheral blood mononuclear cells from GCA patients expressed higher IL-22 transcript than healthy subjects. After stimulation in vitro with phorbol 12-myristate 13-acetate and ionomycin, the frequencies of Th22 and IL-22+ CD4+ lymphocytes were similar between patients with and without GCA. Treatment with IL-22 of primary cultures obtained from TABs increased cell viability under stress conditions and expression of B-cell activating factor. Conclusion IL-22 is increased in patients with GCA and affects viability and gene expression of arterial cells, supporting a potential role in disease pathogenesis.

10.1093/rheumatology/kex334http://hdl.handle.net/10447/245703